if flu makes 1-10 mutations per replication, then why do we onlysee 40 mutations per year ? and flu is even known to mutate much.Most mutations are synonymous, so are even those usually eliminatedby selection ?

http://www.virology.ws profvrr

Two reasons. First, not every change in the RNA (mutation) makes itinto viruses. Some are lethal, for example. Second, sequencing onlyprovides information on the consensus of the population. There aremany genome changes not detected by sequencing because they are atsub-detectable levels in the population. Some believe that in anyvirus preparation there is no single particle that has the same genomesequence as the consensus determined by sequence analyses.

Ngunjiri_JM

I like Prof. Racaniello's explanation. This poses a question: is valied to associate phenotypic changes of influenza virus or other RNA viruses on the basis of single amino acid substitutions?

If most viruses have at least one mutation after one replication cycle,then even moster have at least one after 2 or more replication cyclesand almost all should be mutated after 2-3 days, the average timeto reach a new host.

Unless selection eliminates the synonymously mutated virusesor the mutation rate is much lower.

The mutations should accumulate in the next host,etc.Just wait a year until you sequence to see the then dominant variation.

http://www.virology.ws profvrr

You are not listening to what I am saying. First, forget about aminoacid changes. Think only about mutations – changes in the RNA. Thenrealize that when you sequence a viral RNA, you are getting aconsensus which is not present in any given virus genome. Thediversity is so great that it is not reflected in the sequence that weobtain by chemical methods. Therefore it's not possible to use thesequence that we obtain from viral isolates to see what is reallygoing on in terms of variation.

gsgs

OK, 85% of mutations are synonymous _because_ ~90% of non-synonymous mutationsdon't survive selection.So, ~70% of mutations are non-synonymous but only ~5% of these, 3.5% in total survive.While ~30% of mutations are synonymous (3rd codon) and ~75% of these , 23% in total surive,and we observe 6 times more synonymous mutations than non-synonymous.75% of mutations dieWe observe 40 per genome of 13000 nucleotides per year,that makes 2*10^-6 surviving mutations per nucleotide per cycle of 6hours.Or ~8*10^-6 total mutations including non-surviving.Still much less than the mentioned 2*10^-4

gsgs

but mutations do accumulate in the nect cycle, the next host, regardless of the consensus.Just what virus happens to make it. At that point the mutated virus becames thenew consensus. So, when you sequence after a big number of several cycles, then your old consensus is gone.

If most viruses have at least one mutation after one replication cycle,then even moster have at least one after 2 or more replication cyclesand almost all should be mutated after 2-3 days, the average timeto reach a new host.

Unless selection eliminates the synonymously mutated virusesor the mutation rate is much lower.

The mutations should accumulate in the next host,etc.Just wait a year until you sequence to see the then dominant variation.

http://www.virology.ws profvrr

You are not listening to what I am saying. First, forget about aminoacid changes. Think only about mutations – changes in the RNA. Thenrealize that when you sequence a viral RNA, you are getting aconsensus which is not present in any given virus genome. Thediversity is so great that it is not reflected in the sequence that weobtain by chemical methods. Therefore it's not possible to use thesequence that we obtain from viral isolates to see what is reallygoing on in terms of variation.

gsgs

OK, 85% of mutations are synonymous _because_ ~90% of non-synonymous mutationsdon't survive selection.So, ~70% of mutations are non-synonymous but only ~5% of these, 3.5% in total survive.While ~30% of mutations are synonymous (3rd codon) and ~75% of these , 23% in total surive,and we observe 6 times more synonymous mutations than non-synonymous.75% of mutations dieWe observe 40 per genome of 13000 nucleotides per year,that makes 2*10^-6 surviving mutations per nucleotide per cycle of 6hours.Or ~8*10^-6 total mutations including non-surviving.Still much less than the mentioned 2*10^-4

gsgs

but mutations do accumulate in the nect cycle, the next host, regardless of the consensus.Just what virus happens to make it. At that point the mutated virus becames thenew consensus. So, when you sequence after a big number of several cycles, then your old consensus is gone.